This program project grant, entitled "Models of estrogen action in Alzheimer disease," addresses age changes in brain cell responses to sex steroids that are pertinent to Alzheimer disease, with a focus on estradiol (E2). The five projects investigate components of the general pathway of E2 effects on astrocytes and neurons, using mice that lack sex steroid receptors or src. Project 1: Astrocytes, estradiol, and aging in hippocampal plasticity; C Finch and I Rozovsky Project 2: Estrogenic steroids: neurotrophic action and mechanism; R Brinton and T Berger Project 3: Sex hormones, synaptic plasticity, aging and stress; R Thompson and M Foy Project 4: Estrogen and glutamate receptors in plasticity and AD; M Baudry Project 5: Androgens and neuroprotection in AD models; C Pike Core A ( Finch) includes a Biostatistics Module and Database (D Lavond) for data obtained on the same animals by separate projects Core B (Animals, Finch) provides aging rodents of defined hormonal status (Sprague-Dawley rats; C57BL/6J mice) and genotyped mutant and knockout mice (Er-alpha-KO, Er-beta-KO, Tfm (mutant androgen receptor), and src-KO).